Resorbable pouches for implantable medical devices

ABSTRACT

Biodegradable and resorbable polymer pouches are described for use with cardiac rhythm mamagent devices (CRMs) and other implantable medical devices (IMDs), i.e., a pouch, covering, or other receptacle capable of encasing, surrounding and/or holding the CRM or other IMD for the purpose of securing it in position, inhibiting or reducing bacterial growth, providing pain relief and/or inhibiting scarring or fibrosis on or around the CRM or other IMD. Optionally, the biodegradable and resorbable pouches of the invention include one or more drugs in the polymer matrix to provide prophylactic effects and alleviate side effects or complications associated with the surgery or implantation of the CRM or other IMD.

This application claims priority under 35 U.S.C. §119(e)(5) to U.S.Provisional Patent Application No. 60/864,597, filed Nov. 6, 2006, whichis incorporated herein by reference.

FIELD OF THE INVENTION

Biodegradable and resorbable polymer pouches are described for use withcardiac rhythm management devices (CRMs) and other implantable medicaldevices (IMDs), i.e., a pouch, covering, or other receptacle capable ofencasing, surrounding and/or holding the CRM or other IMD for thepurpose of securing it in position, inhibiting or reducing bacterialgrowth, providing pain relief and/or inhibiting scarring or fibrosis onor around the CRM or other IMD. Optionally, the biodegradable andresorbable pouches of the invention include one or more drugs in thepolymer matrix to provide prophylactic effects and alleviate sideeffects or complications associated with the surgery or implantation ofthe CRM or other IMD.

BACKGROUND OF THE INVENTION

In 1992, it was reported that nosocomial infections involved over 2million patients each year and cost the healthcare systems over 4.5billion dollars annually.¹ Today, these numbers are undoubtedly muchhigher. Surgical site infections, involving approximately 500,000patients, represent the second most common cause of nosocomialinfections and approximately 17% of all hospital-acquired infections.²The incidence of infections associated with the placement of pacemakershas been reported as 0.13 to 19.9% at an average cost of $35,000 totreat these complications which most often involves complete removal ofthe implant.^(3,4)

Post-operative infection is tied to three elements: lack of host defensemechanisms, surgical site and bacteria present at the time of deviceimplantation.⁵ The general health of the patient (i.e., the host factor)is always important; however, since many patients requiring surgery arecompromised in some way—and there is little that can be done to mitigatethat factor—controlling the other two factors becomes important.

Studies have shown that patients are exposed to bacterial contaminationin the hospital, especially in the operating room (OR) and along theroute to the OR.⁶ In fact, bacterial counts of up to 7.0×10⁴ CFU/m² havebeen found in the OR dressing area.⁶ Recent improvements in air handlingand surface cleansing have reduced the environmental levels ofinfectious agents, but not eliminated them. Consequently, further meansto reduce bacterial contamination or to reduce the potential forbacterial infection are desirable.

Controlling the inoculation levels is the third component to the intra-and post-operative surgical infection control triad. One aspect tomicrobial control is the use antibiotics. For example, one practiceadvocates the administration of systemic antibiotics within 60 minutesprior to incision, with additional dosing if the surgery exceeds 3hours.⁵ Such pre-incision administration has shown some positive effectson the incidence of infection associated with the placement ofpacemakers.⁷ An adjunctive approach to managing the potential forimplant contamination has been the introduction of antimicrobial agentson IMDs.^(8,9)

This approach was initially developed to create a barrier to microbialentry into the body via surface-penetrating devices, such as indwellingcatheters,⁹⁻¹¹ The antimicrobial agents were applied in solution as adirect coating on the device to prevent or reduce bacterial colonizationof the device and, therefore, reduce the potential for a device-relatedinfection. While several clinical trials with antimicrobial coatings ondevice surfaces, such as central venous catheters, show reduced devicecolonization and a trend towards reduction of patient infection, theresults have not been statistically significant.¹²⁻¹⁸ Nevertheless,these results are highly relevant since they tend to establish that,with proper aseptic and surgical techniques as well as administration ofappropriate antibiotic therapy, the use of surface-modified devices doeshave a positive impact on the overall procedural/patientoutcome.^(12, 13)

The development of post-operative infection is dependent on manyfactors, and it is not clear exactly how many colony forming units(CFUs) are required to produce clinical infection. It has been reportedthat an inoculation 10³ bacteria at the surgical site produces a woundinfection rate of 20%.⁵ And while current air-handling technology andinfection-control procedures have undoubtedly reduced the microbiallevels in the hospital setting, microbial contamination of animplantable device is still possible. It is known that bacteria, such asStaphylococcus can produce bacteremia within a short time afterimplantation (i.e., within 90 days) with a device or lay dormant formonths before producing an active infection so eradication of thebacterial inoculum at the time of implantation is key and may help toreduce late-stage as well as early-stage device-related infections.²²

For example, the combination of rifampin and minocycline hasdemonstrated antimicrobial effectiveness as a coating for catheters andother implanted devices, including use of those drugs in anon-resorbable coating such as silicone and polyurethane.^(13,19-21) Thecombination of rifampin and minocycline has also been shown to reducethe incidence of clinical infection when used as a prophylactic coatingon penile implants. Additionally, U.S. Ser. No. 60/771,827, filed Feb.8, 2006 and its related cases, describe bioresorbable polymer coating ona surgical mesh as a carrier for the antimicrobial agents (rifampin andminocycline).

The addition of the antimicrobial agents permits the pouch to deliverantimicrobial agents to the implant site and thus to provide a barrierto microbial colonization of the CRM or other IMD during surgicalimplantation as an adjunct to surgical and systemic infection control.

A fully resorbable pouch has advantages over non-resorbable mesheswhich, for example, can become encased with or embedded in dense fibroustissue or present other issues associated with long term foreign bodyexposure. Consequently, when a CRM or other IMD needs replacement, thereplacement surgery can become unduly complicated. Based on this, thepresent invention provides CRM pouches and other IMD made of afully-resorbable material, i.e., biodegradable and resorbable polymersused in the present invention. Such a pouch serves the needs of patientsand practitioners at the time of implantation as well as in the futureif the need arises to remove the CRM or other IMD.

SUMMARY OF THE INVENTION

The pouches of the invention can be fashioned into various sizes andshapes to match the implanted pacemakers, pulse generators, other CRMsand other implantable devices.

As used herein, “pouch,” “pouches,” “pouch of the invention” and“pouches of the invention” means any pouch, bag, skin, shell, covering,or other receptacle formed from a biodegradable polymer or from a anyfully resorbable polymer film and shaped to encapsulate, encase,surround, cover or hold, in whole or in substantial part, an implantablemedical device. The pouches of the invention have openings to permitleads and tubes of the IMD to extend unhindered from the IMD though theopening of the pouch. The pouches may also have porosity to accommodatemonopolar devices that require the IMD to be electrically grounded tothe surrounding tissue. An IMD is substantially encapsulated, encased,surrounded or covered when the pouch can hold the device and at least20%, 30%, 50%, 60%, 75%, 80%, 85%, 90%, 95% or 98% of the device iswithin the pouch or covered by the pouch.

The present invention relates to pouches, coverings and the like madefrom made from fully resorbable and biodegradable polymers which can beformed into films, molded, electrospun and shaped as desired intopouches, bags, coverings, skins, shells or other receptacle and thelike. Pouches of the invention have one or more biodegradable polymersto impart or control drug elution of particular profiles or othertemporary effects.

The polymer matrix of the fully resorbable pouches can comprise one ormore drugs. Such drugs include, but are not limited to, antimicrobialagents, anti-fibrotic agents, anesthetics and anti-inflammatory agentsas well as other classes of drugs, including biological agents such asproteins, growth inhibitors and the like.

The resorbable polymer matrices of the invention are capable ofreleasing one or more drugs into surrounding bodily tissue and proximalto the device such that the drug reduces or prevents implant- orsurgery-related complications. For example, by including an anestheticagent,such that the agent predictably seeps or elutes into thesurrounding bodily tissue, bodily fluid, or systemic fluid, one has auseful way to attenuate the pain experienced at implantation site. Inanother example, replacing the anesthetic agent with ananti-inflammatory agent provides a way to reduce the swelling andinflammation associated implantation of the device and/or pouch. In yetanother example, by delivering an antimicrobial agent in the same mannerand at a therapeutically-effective dose, one has a way to provide a rateof drug release sufficient to prevent colonization of the pouch, the CRMor other IMD, and/or the surgical implantation site by bacteria for atleast the period following surgery necessary for initial healing of thesurgical incision.

Hence, the fully resorbable polymer pouches can be formed and shaped toencapsulate, encase or surround a pacemaker, a defibrillator orgenerator, an implantable access system, a neurostimulator, a drugdelivery pump (e.g., intrathecal delivery system or a pain pump) or anyother IMD for the purpose of securing those devices in position,providing pain relief, inhibiting scarring or fibrosis and/or forinhibiting bacterial growth on or in the tissue surrounding the device.Films are formed into an appropriate shape to hold the IMD.

In accordance with the invention, “fully resorbable polymer film” or“films” is used as a convenient reference to poured films, molded films,sheets, electrospun films, electrospun forms, any form, shape or filmmade by any other technique, no matter how those entities (i.e.,“films”) are made including by pre-forming a shape, injection molding,compression molding, dipping, spraying, electrospinning, thermoformingand the like. The fully resorbable polymer films are made from one ormore fully resorbable, biodegradable polymers and are formed into apouch, covering, skin, shell, receptacle, or other shape suitable forthe IMD to encapsulate, encase or otherwise surround and hold, wholly orin substantial part, an IMD. Further, any of these films can be madeporous, and the percentage to which they cover the IMD can be adjustedby punching holes, piercing the film (before or after shaping) orforming holes (see, e.g., FIGS. 3 and 4 below).

The pouches of the invention can deliver multiple drugs from one or moreindependent layers, some of which may contain no drug.

The invention thus provides a method of delivering drugs at controlledrates and for set durations of time using biodegradable, resorbablepolymers.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of a fully resorbable CRM pouch.

FIG. 2 is a picture of a fully resorbable CRM pouch, wherein the polymermatrix contains antimicrobial agents.

FIG. 3A and 3B is a drawing of a resorbable clamshell-type pouch sizedfor a neurostimulator device, showing top, bottom and side viewsthereof.

FIG. 4A and 4B depicts two views of an aluminum mold used to form aresorbable clamshell-type pouch. The clamshell shape is designed toencase the IMD, has a ridge for folding (or can be easily folded over sothat the sides interlock and the two halves fit snugly together.Additionally the clamshell has a space to allow the leads from thedevice to pass through the clamshell.

DETAILED DESCRIPTION OF THE INVENTION

The pouches of the invention comprise one or more biodegradablepolymers, optionally in layers, and each layer independently furthercontaining one or more drugs. The physical, mechanical, chemical, andresorption characteristics of the polymer enhance the clinicalperformance of the pouch and the surgeon's ability to implant a CRM orother IMD.

These characteristics are accomplished by choosing a suitable thicknessfor the pouch and one or more biodegradable polymer. It is preferred touse biodegradable polymers with a molecular weight between about 10,000and about 200,000 Daltons. Such polymers degrade at rates that maintainsufficient mechanical and physical integrity over at least one 1 week at37° C. in an aqueous environment.

Additionally, the biodegradable polymer has a chemical compositioncomplementary to the drug so that the polymer layer can contain between2-50% drug at room temperature. In one embodiment, the pouch releasesdrug for at least 2-3 days. Such release is preferred, for example, whenthe drug is an analgesic to aide in localized pain management at thesurgical site.

To achieve an analgesic affect, the anesthetic and/or analgesic shouldbe delivered to the injured tissue shortly after surgery or tissueinjury. A drug or drugs for inclusion in the pouches of the inventioninclude, but are not limited to analgesics, anti-inflammatory agents,anesthetics, antimicrobial agents, antifungal agents, NSAIDS, otherbiologics (including proteins and nucleic acids) and the like.Antimicrobial and antifungal agents can prevent the pouch, device,and/or the surrounding tissue from being colonized by bacteria. One ormore drugs are incorporated into the polymer matrix that forms thepouches of the invention.

In another embodiment, the pouch coating comprises an anesthetic suchthat the anesthetic elutes from the implanted pouch to the surroundingtissue of the surgical site for between 1 and 10 days, which typicallycoincides with the period of acute surgical site pain. In anotherembodiment, delivery of an antimicrobial drug via a pouch of theinvention can create an inhibition zone against bacterial growth andcolonization surrounding the implant during the healing process (e.g.,usually about 7-30 days or less) and/or prevent undue fibroticresponses.

Anesthetics that contain amines, such as lidocaine and bupivacaine, arehydrophobic and are difficult to load in sufficient amounts into themost commonly used plastics employed in the medical device industry,such as polypropylene and other non-resorbable thermoplastics. When intheir hydrochloride salt form, anesthetics cannot be effectively loadedin significant concentration into such non-resorbable thermoplasticsbecause of the mismatch in hydrophilicity of the two materials.

Using biodegradable polymers avoids the issue of drug solubility,impregnation or adherence in or to the underlying device by releasingrelatively high, but local, concentrations of those drugs over extendedperiods of time. For example, by modulating the chemical composition ofthe biodegradable polymer, a clinically-efficacious amount of anestheticdrug can be incorporated into a pouch of the invention to assuresufficient drug elution and to provide surgical site, post-operativepain relief for the patient.

Other elution profiles, with faster or slower drug release over adifferent (longer or shorter) times, can be achieved by altering thethickness of the film or the layers that form the pouch, the amount ofdrug in the depot layer and the hydrophilicity of the biodegradablepolymer.

Biodegradable Polymers

The pouches of the invention comprise one or more biodegradablepolymers, and optionally contain one or more drugs. Methods of makingbiodegradable polymers are well known in the art. The biodegradablepolymers suitable for use in the invention include but are not limitedto:

polylactic acid, polyglycolic acid and copolymers and mixtures thereofsuch as poly(L-lactide) (PLLA), poly(D,L-lactide) (PLA);

polyglycolic acid [polyglycolide (PGA)], poly(L-lactide-co-D,L-lactide)(PLLA/PLA), poly(L-lactide-co-glycolide) (PLLA/PGA), poly(D,L-lactide-co-glycolide) (PLA/PGA), poly(glycolide-co-trimethylenecarbonate) (PGA/PTMC), poly(D,L-lactide-co-caprolactone) (PLA/PCL) andpoly(glycolide-co-caprolactone) (PGA/PCL);

polyethylene oxide (PEO), polydioxanone (PDS), polypropylene fumarate,poly(ethyl glutamate-co-glutamic acid),poly(tert-butyloxy-carbonylmethyl glutamate), polycaprolactone (PCL),polycaprolactone co-butylacrylate, polyhydroxybutyrate (PHBT) andcopolymers of polyhydroxybutyrate, poly(phosphazene), poly(phosphateester), poly(amino acid), polydepsipeptides, maleic anhydridecopolymers, polyiminocarbonates, poly[(97.5% dimethyl-trimethylenecarbonate)-co-(2.5% trimethylene carbonate)], poly(orthoesters),tyrosine-derived polyarylates, tyrosine-derived polycarbonates,tyrosine-derived polyiminocarbonates, tyrosine-derived polyphosphonates,polyethylene oxide, polyethylene glycol, polyalkylene oxides,hydroxypropylmethylcellulose, polysaccharides such as hyaluronic acid,chitosan and regenerate cellulose, and proteins such as gelatin andcollagen, and mixtures and copolymers thereof, among others as well asPEG derivatives or blends of any of the foregoing.

In some embodiments, biodegradable polymers of the invention havediphenol monomer units that are copolymerized with an appropriatechemical moiety to form a polyarylate, a polycarbonate, apolyiminocarbonate, a polyphosphonate or any other polymer.

The preferred biodegradable polymers are tyrosine-based polyarylatesincluding those described in U.S. Pat. Nos. 4,980449; 5,099,060;5,216,115; 5,317,077; 5,587,507; 5,658,995; 5,670,602; 6,048,521;6,120,491; 6,319,492; 6,475,477; 6,602,497; 6,852,308; 7,056,493;RE37,160E; and RE37,795E; as well as those described in U.S. PatentApplication Publication Nos. 2002/0151668; 2003/0138488; 2003/0216307;2004/0254334; 2005/0165203; and those described in PCT Publication Nos.WO99/52962; WO 01/49249; WO 01/49311; WO03/091337. These patents andpublications also disclose other polymers containing tyrosine-deriveddiphenol monomer units or other diphenol monomer units, includingpolyarylates, polycarbonates, polyiminocarbonates, polythiocarbonates,polyphosphonates and polyethers.

Likewise, the foregoing patents and publications describe methods formaking these polymers, some methods of which may be applicable tosynthesizing other biodegradable polymers. Finally, the foregoingpatents and publications also describe blends and copolymers withpolyalkylene oxides, including polyethylene glycol (PEG). All suchpolymers are contemplated for use in the present invention.

The representative structures for the foregoing polymers are provide inthe above-cited patents and publications which are incorporated hereinby reference.

As used herein, DTE is the diphenol monomer desaminotyrosyl-tyrosineethyl ester; DTBn is the diphenol monomer desaminotyrosyl-tyrosinebenzyl ester; DT is the corresponding free acid form, namelydesaminotyrosyl-tyrosine. BTE is the diphenol monomer 4-hydroxy benzoicacid-tyrosyl ethyl ester; BT is the corresponding free acid form, namely4-hydroxy benzoic acid-tyrosine.

P22 is a polyarylate copolymer produced by condensation of DTE withsuccinate. P22-10, P22-15, P22-20, P22-xx, etc., represents copolymersproduced by condensation of (1) a mixture of DTE and DT using theindicated percentage of DT (i.e.,10, 15, 20 and xx% DT, etc.) with (2)succinate.

Additional preferred polyarylates are copolymers ofdesaminotyrosyl-tyrosine (DT) and an desaminotyrosyl-tyrosyl ester (DTester), wherein the copolymer comprises from about 0.001% DT to about80% DT and the ester moiety can be a branched or unbranched alkyl,alkylaryl, or alkylene ether group having up to 18 carbon atoms, anygroup of which can, optionally have a polyalkylene oxide therein.Similarly, another group of polyarylates are the same as the foregoingbut the desaminotyrosyl moiety is replaced by a 4-hydroxybenzoyl moiety.Preferred DT or BT contents include those copolymers with from about 1%to about 30%, from about 5% to about 30% from about 10 to about 30% DTor BT. Preferred diacids (used in forming the polyarylates) includesuccinate, glutarate, adipate and glycolic acid.

Additional biodegradable polymers useful for the present invention arethe biodegradable, resorbable polyarylates and polycarbonates disclosedin U.S. provisional application Ser. No. 60/733,988, filed Nov. 3, 2005and in its corresponding PCT Appln. No. PCT/US06/42944, filed Nov. 3,2006. These polymers, include, but are not limited to, BTE glutarate,DTM glutarate, DT propylamide glutarate, DT glycineamide glutarate, BTEsuccinate, BTM succinate, BTE succinate PEG, BTM succinate PEG, DTMsuccinate PEG, DTM succinate, DT N-hydroxysuccinimide succinate, DTglucosamine succinate, DT glucosamine glutarate, DT PEG ester succinate,DT PEG amide succinate, DT PEG ester glutarate and DT PEG estersuccinate.

In a preferred embodiment, the polyarylates are the DTE-DT succinatefamily of polymers, e.g., the P22-xx family of polymers having from5-40% DT, including but not limited to, about 1, 2, 5, 10, 15, 20, 25,27.5, 30, 35 and 40% DT.

Additionally, any of the foregoing polymers used in the presentinvention can have from 0.1-99.9% PEG diacid or any other polyalkyleneoxide diacid, see e.g., U.S. provisional application Ser. No.60/733,988, filed Nov. 3, 2005, its corresponding PCT application, filedNov. 3, 2006 and U.S. Ser. No. 60/983,108, filed Oct. 26, 2007, each ofwhich are incorporated herein by reference. Blends of polyarylates orother biodegradable polymers with polyarylates are also preferred.

The fully resorbable polymer pouches of the invention are prepared usingany of the foregoing biodegradable polymers, and preferably using anyone or more of the tyrosine-based polyarylates described above. Suchpolymers are dissolved in appropriate solvents to cast films, preparespray coating solutions, electrospinning solutions, molding solutionsand the like for forming a fully resorbable polymer film of theinvention.

Fully resorbable pouches, as films, meshes, non-wovens and the like, canbe created by several means: by spray coating a substrate, thermal orsolvent casting, weaving, knitting or electrospinning, dip coating,extrusion, or molding. Sheets can be formed into a pouch configurationby thermoforming, or mechanical forming and heat setting, or adhesive,thermal or ultrasonic assembly. Pouches can be constructed directly fromresorbable polymer by dip or spray coating a pre-formed shape, orinjection or compression molding into the finished shape.

The biodegradable polymers can be formed into multi-layered fullyresorbable polymer films, each layer containing the same or differentpolymers, the same or different drugs, and the same or different amountsof polymers or drugs. For example, a first film layer can contain drug,while the film layer coating layer contains either no drug or a lowerconcentration of drug. For example, a multilayer film can be made bycasting a first layer, allowing it to dry, and casting a second orsuccessive layer onto the first layer, allowing each layer to dry beforecasting the next layer.

The pouches can be shaped to fit relatively snugly or more looselyaround an IMD. For example, the clamshell shaped pouch shown in FIGS. 3and 4 is designed to encase the IMD, is capable of being folded, andeach half interlocks with the other half to secure the shell around thedevice and hold the device within the clamshell. Additionally, theclamshell has a space or opening sufficient to allow the leads from thedevice to pass through the clamshell. The number of spaces or opening inthe pouch that are provided can match the number and placement of theleads or other tubes extending from the CRM or other IMD, as applicablefor the relevant device. The pouches are constructed with polymers fromthe group described herein that are selected to have elastomericproperties if is desirable to have a pouch that fits tightly over theIMD.

The films can be laser cut to produce the desired shaped and sizedpouches, coverings and the like. Two pieces can be sealed, by heat, byultrasound or other method known in the art, leaving one side open topermit insertion of the device at the time of the surgical procedure.

In preferred embodiments, the shape and size of the pouch of theinvention is similar to that of the DRM or IMD with which it is beingused, and the pouch as a sufficient number of openings or spaces toaccommodate the leads or tubings of the particular CRM or other IMD.

The pouches of the invention can be porous. As shown in FIGS. 1 and 2,porous pouches can be formed by punching holes or laser cutting holes inthe films that form the pouch. Porous pouches can also by forming wovenor non-woven fibers made from the biodegradable polymers into pouches.Depending on the fibers and the weave, such pouches may be microporous.As an example, the pouch need not completely encase or surround the IMD.An IMD is thus substantially encapsulated, encased, surrounded orcovered when the pouch can hold the device and at least 20%, 30%, 50%,60%, 75%, 80%, 85%, 90%, 95% or 98% of the device is within the pouch.Porous pouches and partially encased pouches permit contact with tissueand body fluids and are particularly useful with monopole CRM or otherIMD devices. Porosity will contribute to the percentage of the IMDcovered by the pouch. That is, an IMD is considered to be 50% covered ifit is completely surrounded by a pouch that is constructed of a filmwith 50% voids or holes.

Drugs

Any drug, biological agent or active ingredient compatible with theprocess of preparing the pouches of the invention can be incorporatedinto the pouch or into one or more layers of the biodegradable polymerlayers that form a pouch of the invention. Doses of such drugs andagents are known in the art. Those of skill in the art can readilydetermine the amount of a particular drug to include in the Pouches ofthe invention.

Examples of drugs suitable for use with the present invention includeanesthetics, antibiotics (antimicrobials), anti-inflammatory agents,fibrosis-inhibiting agents, anti-scarring agents, leukotrieneinhibitors/antagonists, cell growth inhibitors and the like. As usedherein, “drugs” is used to include all types of therapeutic agents,whether small molecules or large molecules such as proteins, nucleicacids and the like. The drugs of the invention can be used alone or incombination.

Any pharmaceutically acceptable form of the drugs of the presentinvention can be employed in the present invention, e.g., the free baseor a pharmaceutically acceptable salt or ester thereof. Pharmaceuticallyacceptable salts, for instance, include sulfate, lactate, acetate,stearate, hydrochloride, tartrate, maleate, citrate, phosphate and thelike.

Examples of non-steroidal anti-inflammatories include, but are notlimited to, naproxen, ketoprofen, ibuprofen as well as diclofenac;celecoxib; sulindac; diflunisal; piroxicam; indomethacin; etodolac;meloxicam; r-flurbiprofen; mefenamic; nabumetone; tolmetin, and sodiumsalts of each of the foregoing; ketorolac bromethamine; ketorolacbromethamine tromethamine; choline magnesium trisalicylate; rofecoxib;valdecoxib; lumiracoxib; etoricoxib; aspirin; salicylic acid and itssodium salt; salicylate esters of alpha, beta, gamma-tocopherols andtocotrienols (and all their d, 1, and racemic isomers); and the methyl,ethyl, propyl, isopropyl, n-butyl, sec-butyl, t-butyl, esters ofacetylsalicylic acid.

Examples of anesthetics include, but are not limited to, licodaine,bupivacaine, and mepivacaine. Further examples of analgesics,anesthetics and narcotics include, but are not limited to acetaminophen,clonidine, benzodiazepine, the benzodiazepine antagonist flumazenil,lidocaine, tramadol, carbamazepine, meperidine, zaleplon, trimipraminemaleate, buprenorphine, nalbuphine, pentazocain, fentanyl, propoxyphene,hydromorphone, methadone, morphine, levorphanol, and hydrocodone. Localanesthetics have weak antibacterial properties and can play a dual rolein the prevention of acute pain and infection.

Examples of antimicrobials include, but are not limited to, triclosan,chlorhexidine, rifampin, minocycline (or other tetracycline derivative),vancomycin, gentamycin, cephalosporins and the like. In preferredembodiments the coatings contain rifampin and another antimicrobialagent, especially a tetracycline derivative. In another preferredembodiment, the coatings contains a cephalosporin and anotherantimicrobial agent. Preferred combinations include rifampin andminocycline, rifampin and gentamycin, and rifampin and minocycline.

Further antimicrobials include aztreonam; cefotetan and its disodiumsalt; loracarbef; cefoxitin and its sodium salt; cefazolin and itssodium salt; cefaclor; ceftibuten and its sodium salt; ceftizoxime;ceftizoxime sodium salt; cefoperazone and its sodium salt; cefuroximeand its sodium salt; cefuroxime axetil; cefprozil; ceftazidime;cefotaxime and its sodium salt; cefadroxil; ceftazidime and its sodiumsalt; cephalexin; cefamandole nafate; cefepime and its hydrochloride,sulfate, and phosphate salt; cefdinir and its sodium salt; ceftriaxoneand its sodium salt; cefixime and its sodium salt; cefpodoxime proxetil;meropenem and its sodium salt; imipenem and its sodium salt; cilastatinand its sodium salt; azithromycin; clarithromycin; dirithromycin;erythromycin and hydrochloride, sulfate, or phosphate saltsethylsuccinate, and stearate forms thereof; clindamycin; clindamycinhydrochloride, sulfate, or phosphate salt; lincomycin and hydrochloride,sulfate, or phosphate salt thereof; tobramycin and its hydrochloride,sulfate, or phosphate salt; streptomycin and its hydrochloride, sulfate,or phosphate salt; vancomycin and its hydrochloride, sulfate, orphosphate salt; neomycin and its hydrochloride, sulfate, or phosphatesalt; acetyl sulfisoxazole; colistimethate and its sodium salt;quinupristin; dalfopristin; amoxicillin; ampicillin and its sodium salt;clavulanic acid and its sodium or potassium salt; penicillin G;penicillin G benzathine, or procaine salt; penicillin G sodium orpotassium salt; carbenicillin and its disodium or indanyl disodium salt;piperacillin and its sodium salt; ticarcillin and its disodium salt;sulbactam and its sodium salt; moxifloxacin; ciprofloxacin; ofloxacin;levofloxacins; norfloxacin; gatifloxacin; trovafloxacin mesylate;alatrofloxacin mesylate; trimethoprim; sulfamethoxazole; demeclocyclineand its hydrochloride, sulfate, or phosphate salt; doxycycline and itshydrochloride, sulfate, or phosphate salt; minocycline and itshydrochloride, sulfate, or phosphate salt; tetracycline and itshydrochloride, sulfate, or phosphate salt; oxytetracycline and itshydrochloride, sulfate, or phosphate salt; chlortetracycline and itshydrochloride, sulfate, or phosphate salt; metronidazole; dapsone;atovaquone; rifabutin; linezolide; polymyxin B and its hydrochloride,sulfate, or phosphate salt; sulfacetamide and its sodium salt; andclarithromycin.

Examples of antifungals include amphotericin B; pyrimethamine;flucytosine; caspofungin acetate; fluconazole; griseofulvin; terbinafinand its hydrochloride, sulfate, or phosphate salt; ketoconazole;micronazole; clotrimazole; econazole; ciclopirox; naftifine; anditraconazole.

Other drugs that can be incorporated into the coatings on the meshpouches of the invention include, but are not limited to, keflex,acyclovir, cephradine, malphalen, procaine, ephedrine, adriamycin,daunomycin, plumbagin, atropine, quinine, digoxin, quinidine,biologically active peptides, cephradine, cephalothin,cis-hydroxy-L-proline, melphalan, penicillin V, aspirin, nicotinic acid,chemodeoxycholic acid, chlorambucil, paclitaxel, sirolimus,cyclosporins, 5-flurouracil and the like.

Additional, drugs include those that act as angiogenensis inhibitors orinhibit cell growth such as epidermal growth factor, PDGF, VEGF, FGF(fibroblast growth factor) and the like. These drugs include anti-growthfactor antibodies (neutrophilin-1), growth factor receptor-specificinhibitors such as endostatin and thalidomide.

Examples of anti-inflammatory compound include, but are not limited to,anecortive acetate; tetrahydrocortisol,4,9(11)-pregnadien-17.alpha.,21-diol-3,20-dione and its -21-acetatesalt; 11-epicortisol; 17.alpha.-hydroxyprogesterone;tetrahydrocortexolone; cortisona; cortisone acetate; hydrocortisone;hydrocortisone acetate; fludrocortisone; fludrocortisone acetate;fludrocortisone phosphate; prednisone; prednisolone; prednisolone sodiumphosphate; methylprednisolone; methylprednisolone acetate;methylprednisolone, sodium succinate; triamcinolone;triamcinolone-16,21-diacetate; triamcinolone acetonide and its-21-acetate, -21-disodium phosphate, and -21-hemisuccinate forms;triamcinolone benetonide; triamcinolone hexacetonide; fluocinolone andfluocinolone acetate; dexamethasone and its -21-acetate,-21-(3,3-dimethylbutyrate), -21-phosphate disodium salt,-21-diethylaminoacetate, -21-isonicotinate, -21-dipropionate, and-21-palmitate forms; betamethasone and its -21-acetate, -21-adamantoate,-17-benzoate, -17,21-dipropionate, -17-valerate, and -21-phosphatedisodium salts; beclomethasone; beclomethasone dipropionate;diflorasone; diflorasone diacetate; mometasone furoate; andacetazolamide.

Examples of leukotriene inhibitors/antagonists include, but are notlimited to, leukotriene receptor antagonists such as acitazanolast,iralukast, montelukast, pranlukast, verlukast, zafirlukast, andzileuton.

Another useful drug that can be incorporated into the coatings of theinvention is sodium 2-mercaptoethane sulfonate (Mesna). Mesna has beenshown to diminish myofibroblast formation in animal studies of capsularcontracture with breast implants [Ajmal et al. (2003) Plast. Reconstr.Surg. 112:1455-1461] and may thus act as an anti-fibrosis agent.

CRMs and Other IMDs

The CRMs and other IMDs used with the pouches of the invention includebut are not limited to pacemakers, defibrillators, implantable accesssystems, neurostimulators, other stimulation devices, ventricular assistdevices, infusion pumps or other implantable devices (or implantablecomponents thereof) for delivering medication, hydrating solutions orother fluids, intrathecal delivery systems, pain pumps, or any otherimplantable system to provide drugs or electrical stimulation to a bodypart.

Implantable cardiac rhythm management devices (CRMs) are a form of IMDsand are life-long medical device implants. CRMs ensure the heartcontinually beats at a steady rate. There are two main types of CRMdevices: implantable cardiac rhythm management devices and implantabledefibrillators.

The ICDs, or implantable cardioverter defibrillator, and pacemakersshare common elements. They are permanent implants inserted throughrelatively minor surgical procedures. Each has 2 basic components: agenerator and a lead. The generator is usually placed in a subcutaneouspocket below the skin of the breastbone and the lead is threaded downand into the heart muscle or ventricle. The common elements of placementand design result in shared morbidities, including lead extrusion,lead-tip fibrosis, and infection. Although infection rates arepurportedly quite low, infection is a serious problem as any bacterialcontamination of the lead, generator, or surgical site can traveldirectly to the heart via bacterial spreading along the generator andleads. Endocarditis, or an infection of the heart, has reportedmortality rates as high as 33%.

An ICD is an electronic device that constantly monitors heart rate andrhythm. When it detects a fast, abnormal heart rhythm, it deliversenergy to the heart muscle. This action causes the heart to beat in anormal rhythm again in an attempt to return it to a sinus rhythm.

The ICD has two parts: the lead(s) and a pulse generator. The lead(s)monitor the heart rhythm and deliver energy used for pacing and/ordefibrillation (see below for definitions). The lead(s) are directlyconnected to the heart and the generator. The generator houses thebattery and a tiny computer. Energy is stored in the battery until it isneeded. The computer receives information on cardiac function via theleads and reacts to that information on the basis of its programming.

The different types of ICDs include, but are not limited to, singlechamber ICDs in which a lead is attached in the right ventricle. Ifneeded, energy is delivered to the ventricle to help it contractnormally; dual chamber ICDs in which the leads are attached in the rightatrium and the right ventricle. Energy is delivered first to the rightatrium and then to the right ventricle to ensure that the heart beats ina normal sequence; and biventricular ICDs in which leads are attached inthe right atrium, the right ventricle and the left ventricle. Thisarrangement helps the heart beat in a more balanced way and isspecifically used for patients with heart failure.

A pacemaker is a small device that sends electrical impulses to theheart muscle to maintain a suitable heart rate and rhythm. A pacemakercan also be used to treat fainting spells (syncope), congestive heartfailure, and hypertrophic cardiomyopathy. Pacemakers are generallyimplanted under the skin of the chest during a minor surgical procedure.The pacemaker is also comprised of leads and a battery-driven pulsegenerator. The pulse generator resides under the skin of the chest. Theleads are wires that are threaded through the veins into the heart andimplanted into the heart muscle. They send impulses from the pulsegenerator to the heart muscle, as well as sense the heart's electricalactivity.

Each impulse causes the heart to contract. The pacemaker may have one tothree leads, depending on the type of pacemaker needed to treat yourheart problem.

The different types of pacemakers include, but are not limited to singlechamber pacemakers which use one lead in the upper chambers (atria) orlower chambers (ventricles) of the heart; dual chamber pacemakers whichuse one lead in the atria and one lead in the ventricles of your heart;and biventricular pacemakers which use three leads: one placed in theright atrium, one placed in the right ventricle, and one placed in theleft ventricle (via the coronary sinus vein).

The pouches of the invention can thus be designed to fit a wide range ofpacemakers and implantable defibrillators from a variety ofmanufacturers (see Table 1). Sizes of the CRMs vary and typically sizeranges are listed in Table 1.

TABLE 1 CRM Devices Size Manufacturer Device Type Model (H″ × L″ × W″)Medtronic EnPulse Pacing Pacing system E2DR01 1.75 × 2 × 0.33 systemMedtronic EnPulse Pacing Pacing system E2DR21 1.75 × 1.63 × 0.33 systemMedtronic EnRhythm Pacing system P1501DR 1.77 × 2 × 0.31 Pacing systemMedtronic AT500 Pacing Pacing system AT501 1.75 × 2.38 × 0.33 systemMedtronic Kappa DR900 Pacing system DR900, DR700 1.75-2 × 1.75-2 × 0.33& 700 series Medtronic Kappa DR900 Pacing system SR900, SR700 1.5-1.75 ×1.75-2 × 0.33 & 700 series Medtronic Sigma Pacing system D300, D200,D303, 1.75 × 2 × 0.33 D203 Medtronic Sigma Pacing system DR300, DR200,1.75-2 × 2 × 0.33 DR303, DR306, DR203 Medtronic Sigma Pacing systemVDD300, VDD303 1.75 × 1.75 × 0.33 Medtronic Sigma Pacing system S300,S200, S100, 1.63 × 2 × 0.33 S303, S203, S103, S106, VVI-103 MedtronicSigma SR Pacing system SR300, S200, 1.63 × 2 × 0.33 SR303, SR306, SR203Medtronic Entrust Defibrillator D154VRC 35J 2.44 × 2 × 0.6 MedtronicMaximo & Defibrillator Size of a pager Marquis family Medtronic Gemfamily Defibrillator III T, III R, III R, II Size of a pager R, II VRGuidant Contak Renewal Pacing system H120, H125 2.13 × 1.77 × 033 TR St.Jude Identity Pacing system ADx DR, ADx SR, 1.6-1.73 × 1.73-2.05 × 0.24ADx XL, ADx VDR St. Jude Integrity Pacing system ADx DR, ADx SR 1.6-1.73× 1.73-2.05 × 0.24

Implantable neurostimulators are similar to pacemakers in that thedevices generate electrical impulses. These devices send electricalsignals via leads to the spine and brain to treat pain and otherneurological disorders. For example, when the leads are implanted in thespine, the neurostimulation can be used to treat chronic pain(especially back and spinal pain); when the leads are implanted in thebrain, the neurostimulation can be used to treat epilepsy and essentialtremor including the tremors associated with Parkinson's disease andother neurological disorders. Neurostimulation can be used to treatsevere, chronic nausea and vomiting as well as urological disorders. Forthe former, electrical impulses are sent to the stomach; for the latter,the electrical impulses are sent to the sacral nerves in the lower back.The implant location of the neurostimulator varies by application but,in all cases, is placed under the skin and is susceptible to infectionat the time of implantation and pos-implantation. Likewise,reintervention and replacement of batteries in the neurostimulators canoccur at regular intervals.

The pouches of the invention can thus be designed to fit a wide range ofneurostimulators from a variety of manufacturers (see Table 2). Sizes ofthe neurostimulators vary and typically size ranges are listed in Table2.

TABLE 2 Neurostimulators Size Manufacturer Device Type Model (H″ × L″ ×W″) Medtronic InterStim Neurostimulation 3023 2.17 × 2.4 × 0.39 INSMedtronic InterStim Neurostimulation 3058 1.7 × 2.0 × 0.3 INS IIMedtronic RESTORE Neurostimulation 37711 2.56 × 1.93 × 0.6 AdvancedPrecision Neurostimulation/Spinal 2.09 × 1.70 × 0.35 Bionics IPG CordStimulator (Boston Scientific) Cyberonics VNS Neurostimulation/Epilepsy102 2.03 × 2.06 × 0.27 Therapy system Cyberonics VNSNeurostimulation/Epilepsy 102R 2.03 × 2.32 × 0.27 Therapy system ANS(St. Jude) Eon Neurostimulation Comparable to Medtronic Restore ANS (St.Jude) Genesis RC Neurostimulation Comparable to Medtronic Restore ANS(St. Jude) Genesis XP Neurostimulation Comparable to Medtronic Restore

Reported infection rates for first implantation are usually quite low(less than 1%); however, they increase dramatically when areintervention is necessary. Reintervention often requires the removalof the generator portion of the ICD, pacemaker, neurostimulator, drugpump or other IMD and having a resorbable pouch enhances that process.

Other IMDs for use in the invention are drug pumps, especially painpumps and intrathecal delivery systems. These devices generally consistof an implantable drug pump and a catheter for dispensing the drug. Theimplantable drug pump is similar in size to the neurostimulators andCRMs. Further implantable medical devices include, but are not limitedto, implantable EGM monitors, implantable access systems, or any otherimplantable system that utilizes battery power to provide drugs orelectrical stimulation to a body part.

Antimicrobial Efficacy

Antimicrobial efficacy of the pouches of the invention can bedemonstrated in laboratory (in vitro), for example, using the modifiedKirby-Bauer Antibiotic Susceptibility Test (Disk Diffusion Test) (invitro) to assess bacterial zones of inhibitions or by the Anti-microbialFinishes Method to access the reduction in bacteria achieved with thepouch (in vitro). In such experiments, a small disk of the pouch is cutand used. Antimicrobial efficacy can also be demonstrated in vivo usinganimal models of infection. For example, a pouch and device combinationare implanted in an animal, the surgical site is deliberately infectedwith a predetermined level of a pathogenic microorganism, such asStaphylococcus aureus or Staphylococcus epidermis, and the animal ismonitored for signs of infection and inflammation. At sacrifice, theanimal is assessed for inflammation, fibrosis and bacterial colonizationof the pouch (to the extent still present), device and the surroundingtissues.

It will be appreciated by those skilled in the art that variousomissions, additions and modifications may be made to the inventiondescribed above without departing from the scope of the invention, andall such modifications and changes are intended to fall within the scopeof the invention, as defined by the appended claims. All references,patents, patent applications or other documents cited are hereinincorporated by reference.

EXAMPLE 1 Resorbable Pouch

To prepare a resorbable pouch, 18.0 g of polymer, 1.0 g minocycline and1.0 g rifampin are dissolved in 75 mL of a solution oftetrahydrofuran-methanol. This solution is poured over a level non-stickTeflon surface. A calibrated stainless steel gardner knife is used tospread the solution to the desired thickness, typically to a range offrom about 2 and about 400 microns.

The film is dried at ambient temperature overnight. Thereafter, thesolvent cast film is dried in a convection oven at 50° C. for 1 day, thetemperature of the oven is increased to 80° C. and the film is driedfurther for 2 days. At this point, the dried film is ready for lasercutting and further processing to create the pouch, i.e., cutting andsealing three of the sides. The pouch is cut for overall shape to matchthe desired CRM and to create a mesh like covering. A CRM pouch madeusing a DT-DTE succinate polymer is shown in FIG. 4.

EXAMPLE 2 Resorbable Clamshell Pouch

To prepare a resorbable clamshell pouch, a film is prepared as describedabove in Example 1. After the film is dried, it is thermoformed into theclamshell shape by placing a film sheet into a frame and heating thefilm to about 90-100° C. and lowering the frame over a clamshell-shapedmold as shown in FIG. 7 whereby the film takes the shape of theclamshell mold. The molded clamshell is cooled, freed from the mold, andlaser cut from the film sheet.

REFERENCES

-   -   1. Hospital Infections Program, National Centrer for Infectious        Disease, CDC. Public health focus: surveillance, prevention, and        control of nosocomial infections. MMWR Weekly, 1992; 41:783-7.    -   2. Perencevich E N, Sands K E, Cosgrove S E, et. al. Health and        economic impact of surgical site infections diagnosed after        hospital discharge. Emerging Infect Dis, 2003; 9:196-203.    -   3. Baddour L M, Bettmenn M A, Bolger A F, et.al. Nonvalvular        cardiovascular device-related infections. Circulation, 2003;        108:2015-31.    -   4. Darouiche R O, Treatment of infections associated with        surgical implants. NEJM, 2004; 350:1422-9.    -   5. Meakins J L, Prevention of Postoperative Infection. In ACS        Surgery: Principals and Practice.

American College of Surgeons, 2005.

-   -   6. Hambraeus A, Bengtsson S, Laurell G. Bacterial contamination        in a modern operating suite, 2.effect of a zoning system on        contamination of floors and other surfaces. J Hyg, 1978;        80:57-67.    -   7. Da Costa A, Kirkorian G, Cucherat M, et.al. Antibiotic        prophylaxis for permanent pacemaker implantation: a        meta-analysis. Circulation, 1998; 97:1796-1801.    -   8. Darouiche R O, Antimicrobial approaches for preventing        infections associated with surgical implants. Clin Infect Dis        2003; 36:1284-9.    -   9. Pearson M L and Abrutyn E, Reducing the risk for        catheter-related infections: a new strategy. Ann Intern Med,        1997; 127:304-6.    -   10. Donlon R M, Biofilms and device-associated infections. Emerg        Infect Dis, 2001; 7:277-81.    -   11. Maki D G and Tambyah P A, Engineering out the risk of        infection with urinary catheters. Emerg Infect Dis, 2001;        7:342-7.    -   12. Maki D G, Stolz S M, Wheeler S and Mermel L A. Prevention of        central venous catheter-related blood stream infection by use of        an antiseptic-impregnated catheter: a randomized, controlled        trial. Ann Intern Med, 1997:127:257-66.    -   13. Raad I, Darouiche R, Dupuis J, et.al., Central venous        catheters coated with minocycline and rifampin for the        prevention of catheter-related colonization and bloodstream        infections: a randomized, double-blind trial. Ann Intern Med,        1997; 127:267-74.    -   14. Collin G R, Decreasing catheter colonization through the use        of an antiseptic-impregnated catheter: a continuous quality        improvement project. Chest, 1999; 115:1632-40.    -   15. Tennenberg S, Lieser M, McCurdy B, Boomer G, Howington E,        Newman C, Wolf I A prospective randomized trial of an        antibiotic- and antiseptic-coated central venous catheter in the        prevention of catheter-related infections. Arch Surg, 1997;        132:1348-51    -   16. George S J, Vuddamalay P, Boscoe M J. Antiseptic-impregnated        central venous catheters reduce the incidence of bacterial        colonization and associated infection in immunocompromised        transplant patients. Eur J Anaesthesiol, 1997; 14:428-31.    -   17. Segura M, Alvarez-Lerma F, Tellado J M, Jimenez-Ferreres J,        Oms L, Rello J, Baro T, Sanchez R, Morera A, Mariscal D,        Marrugat J, Sitges-Serra A. A clinical trial on the prevention        of catheter-related sepsis using a new hub model. Ann Surg,        1996; 223:363-9.    -   18. Bach A, Schmidt H, Bottiger B, Schreiber B, Bohrer H, Motsch        J, Martin E, Sonntag H G. Retention of antibacterial activity        and bacterial colonization of antiseptic-bonded central venous        catheters. J Antimicrob Chemother, 1996; 37:315-22.    -   19. Li H, Fairfax M R, Dubocq F, et.al. Antibacterial activity        of antibiotic coated silicon grafts. J Urol, 1998; 160: 1910-3.    -   20. Darouiche R O, Mansouri N D, Raad H. Efficacy of        antimicrobial-impregnated silicone sections from penile implants        in preventing device colonization in an animal model. Urology,        2002; 59:303-7.    -   21. Darouiche R O, Meade R, Mansouri N D, Netscher D T. In vivo        efficacy of antimicrobial-impregnated saline-filled silicone        implants. Plast Reconstr Surg, 2002; 109:1352-7.    -   22. Chamis A L, Peterson G E, Cabell C H, et.al. Staphylococcus        aureus bacteremia in patients with permanent pacemakers of        implantable cardioverter-defribrillators. Circulation, 2001;        104:1029-33.

1-12. (canceled)
 13. A kit comprising: an implantable medical deviceunit; and a resorbable pouch comprising a biodegradable and resorbablepolymer formed to at least partially enclose or encase said implantablemedical device unit and one or more drugs.
 14. The kit of claim 13,wherein said medical device unit is a cardiac rhythm management device.15. The kit of claim 13, wherein said medical device unit is apacemaker, a defibrillator, a pulse generator, an implantable accesssystem, a drug pump or a neurostimulator.
 16. The kit of claim 13,wherein said pouch is a thermoformed clamshell type pouch.
 17. The kitof claim 13, wherein said biodegradable and resorbable polymer isselected from the group consisting of a polylactic acid, polyglycolicacid, poly(L-lactide), poly(D,L-lactide), polyglycolic acid,poly(L-lactide-co-D,L-lactide), poly(L-lactide-co-glycolide), poly(D,L-lactide-co-glycolide), poly(glycolide-co-trimethylene carbonate),poly(D,L-lactide-co-caprolactone), poly(glycolide-co-caprolactone),polyethylene oxide, polyoxaester, polydioxanone, polypropylene fumarate,poly(ethyl glutamate-co-glutamic acid),poly(tert-butyloxy-carbonylmethyl glutamate), polycaprolactone,polycaprolactone co-butylacrylate, polyhydroxybutyrate,poly(phosphazene), poly(phosphate ester), poly(amino acid),polydepsipeptide, maleic anhydride copolymer, polyiminocarbonates,poly[(97.5% dimethyl-trimethylene carbonate)-co-(2.5% trimethylenecarbonate)], poly(orthoesters), tyrosine-derived polyarylate,tyrosine-derived polycarbonate, tyrosine-derived polyiminocarbonate,tyrosine-derived polyphosphonate, polyalkylene oxide,hydroxypropylmethylcellulose, polysaccharide, protein, and copolymers,terpolymers and blends of any thereof.
 18. The kit of claim 13, whereinsaid biodegradable and resorbable polymer comprises one or moretyrosine-derived diphenol monomer units.
 19. The kit of claim 13,wherein said one or more drugs are selected from the group consisting ofantimicrobial agents, anesthetics, analgesics, anti-inflammatory agents,anti-scarring agents, anti-fibrotic agents and leukotriene inhibitors.20. The kit of claim 13, wherein said one or more drugs is ananesthetic.
 21. The kit of claim 13, wherein said one or more drugs isan antimicrobial agent.
 22. The kit of claim 21, wherein saidantimicrobial agent is selected from the group consisting of rifampin,minocycline, silver/chlorhexidine, vancomycin, a cephalosporin,gentamycin, triclosan and combinations thereof.
 23. The kit of claim 21,wherein said antimicrobial agent is two antimicrobial agents, saidagents being rifampin and a tetracycline derivative.
 24. The kit ofclaim 13, wherein said pouch is configured to permit ingrowth of tissueinto said pouch to resist post implantation migration of saidimplantable medical device unit.
 25. The kit of claim 13, wherein saidpouch has a porosity sufficient to electrically ground said implantablemedical device unit to tissue surrounding said pouch.
 26. The kit ofclaim 13, wherein said pouch is configured to removably enclose orencase said implantable medical device unit.
 27. The kit of claim 13,wherein said pouch is a thermoformed clamshell type pouch having a firsthalf and a second half connected by a hinge.
 28. The kit of claim 13,wherein said implantable medical device unit is movable within saidpouch prior to implantation of said pouch and is fixed relative to saidpouch following implantation of said pouch.
 29. The kit of claim 13,wherein said pouch is woven or knit from resorbable fibers, or made fromelectrospun resorbable fibers.
 30. The kit of claim 13, wherein saidbiodegradable and resorbable polymer has a molecular weight betweenabout 10,000 and about 20,000 Daltons.
 31. The kit of claim 13, whereinsaid biodegradable and resorbable polymer is a member of the P22-xxfamily.
 32. The kit of claim 13, wherein said biodegradable andresorbable polymer has elastomeric characteristics such that said pouchfits tightly over said implantable medical device unit.